liftsiron
Owner/Admin
- Joined
- Nov 12, 2003
- Messages
- 19,024
Thanks CEM
Myotoxic effects of clenbuterol in the rat heart and soleus muscle.
Burniston JG, Ng Y, Clark WA, Colyer J, Tan LB, Goldspink DF.
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 2ET, United Kingdom. [email protected]
Myocyte-specific necrosis in the heart and soleus muscle of adult male Wistar rats was investigated in response to a single subcutaneous injection of the anabolic beta(2)-adrenergic receptor agonist clenbuterol. Necrosis was immunohistochemically detected by administration of a myosin antibody 1 h before the clenbuterol challenge and quantified by using image analysis. clenbuterol-induced myocyte necrosis occurred against a background of zero damage in control muscles. In the heart, the clenbuterol-induced necrosis was not uniform, being more abundant in the left subendocardium and peaking 2.4 mm from the apex. After position (2.4 mm from the apex), dose (5 mg clenbuterol/kg), and sampling time (12 h) were optimized, maximum cardiomyocyte necrosis was found to be 1.0 +/- 0.2%. In response to the same parameters (i.e., 5 mg of clenbuterol and sampled at 12 h), skeletal myocyte necrosis was 4.4 +/- 0.8% in the soleus. These data show significant myocyte-specific necrosis in the heart and skeletal muscle of the rat. Such irreversible damage in the heart suggests that clenbuterol may be damaging to long-term health.
PMID: 12381771 [PubMed - indexed for MEDLINE]
Characterization of adrenoceptor involvement in skeletal and cardiac myotoxicity Induced by sympathomimetic agents: toward a new bioassay for beta-blockers.
Tan LB, Burniston JG, Clark WA, Ng Y, Goldspink DF.
Academic Unit of Molecular Vascular Medicine, University of Leeds, England.
Excessive levels of catecholamines have long been known to be cardiotoxic, but less well known are their toxic effects on skeletal muscle. By using an antimyosin monoclonal antibody and quantitative methods to measure the extent of myocyte necrosis, and by employing modulators of adrenoceptors (ARs), including clenbuterol, bupranolol, propranolol, bisoprolol, atenolol, ICI-118551, phenoxybenzamine, prazosin, and yohimbine, the involvement of ARs in isoproterenol-induced myotoxicity was characterized. In the myocardium, the toxic effects were predominantly mediated via the beta(1)-ARs. In the soleus muscle, it was almost solely via the beta(2)-ARs. Myotoxicity was also observed in the myocardium when challenged with the beta(2)-AR agonist clenbuterol. This was found to be mediated via sympathetic presynaptic beta(2)-ARs, leading to enhanced release of norepinephrine. This effect was abolished by prior treatment with reserpine. The skeletal muscle was found to be more sensitive to the myotoxic effects than cardiac muscle at lower doses of beta-AR agonists. These experiments introduce a new way of assaying beta-AR antagonists by classifying them according to their ability to prevent catecholamine-induced myotoxicity. Further research along these lines may deepen understanding of which beta-blockers work best in heart failure therapy.
PMID: 12658052 [PubMed - indexed for MEDLINE]
Dose-dependent separation of the hypertrophic and myotoxic effects of the beta(2)-adrenergic receptor agonist clenbuterol in rat striated muscles.
Burniston JG, Clark WA, Tan LB, Goldspink DF.
Research Institute for Sport & Exercise Sciences, Liverpool John Moores University, Webster Street, Liverpool L3 2ET, UK.
Muscle growth in response to large doses (milligrams per kilogram) of beta(2)-adrenergic receptor agonists has been reported consistently. However, such doses may also induce myocyte death in the heart and skeletal muscles and hence may not be safe doses for humans. We report the hypertrophic and myotoxic effects of different doses of clenbuterol. Rats were infused with clenbuterol (range, 1 mug to 1 mg.kg(-1)) for 14 days. Muscle protein content, myofiber cross-sectional area, and myocyte death were then investigated. Infusions of >/=10 mug.kg(-1).d(-1) of clenbuterol significantly (P < 0.05) increased the protein content of the heart (12%-15%), soleus (12%), plantaris (18%-29%), and tibialis anterior (11%-22%) muscles, with concomitant myofiber hypertrophy. Larger doses (100 mug or 1 mg) induced significant (P < 0.05) myocyte death in the soleus (peak 0.2 +/- 0.1% apoptosis), diaphragm (peak 0.15 +/- 0.1% apoptosis), and plantaris (peak 0.3 +/- 0.05% necrosis), and significantly increased the area fraction of collagen in the myocardium. These data show that the low dose of 10 mug.kg(-1).d(-1) can be used in rats to investigate the anabolic effects of clenbuterol in the absence of myocyte death. Muscle Nerve, 2006.
PMID: 16411205 [PubMed - in process]
http://etd.lsu.edu/docs/available/et...son_thesis.pdf
In rats, a single administration of clenbuterol at or above 10?g/kg produces skeletal muscle necrosis, and doses at or above 100?g/kg induce cardiac necrosis8,10,12. In the heart, this effect is most pronounced in the left ventricle. With repeated administration at or below 10?g/kg in rats, clenbuterol appears to induce muscle hypertrophy without adverse side effects; the attenuation of myotoxic effects over time is thought to be related to downregulation of adrenoreceptors10. Skeletal and cardiac muscle injury was demonstrated in both non-surviving horses. The dose of clenbuterol administered to horse 3 was well below the dose which is reported to induce cardiac necrosis in rats.
Cardiac hypertrophy - thickening (enlarging) of the heart muscle - is a side effect of using clenbuterol demonstrated in animal studies. As well, there have been reports of myocardial infarction, or heart attacks, in humans. In two unrelated cases, 2 otherwise healthy body builders aged only 26 and 17 experienced myocardial infarction from the use of clenbuterol. Various studies have also found that prolonged use actually reduced physical performance of the subjects.
Myotoxic effects of clenbuterol in the rat heart and soleus muscle.
Burniston JG, Ng Y, Clark WA, Colyer J, Tan LB, Goldspink DF.
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 2ET, United Kingdom. [email protected]
Myocyte-specific necrosis in the heart and soleus muscle of adult male Wistar rats was investigated in response to a single subcutaneous injection of the anabolic beta(2)-adrenergic receptor agonist clenbuterol. Necrosis was immunohistochemically detected by administration of a myosin antibody 1 h before the clenbuterol challenge and quantified by using image analysis. clenbuterol-induced myocyte necrosis occurred against a background of zero damage in control muscles. In the heart, the clenbuterol-induced necrosis was not uniform, being more abundant in the left subendocardium and peaking 2.4 mm from the apex. After position (2.4 mm from the apex), dose (5 mg clenbuterol/kg), and sampling time (12 h) were optimized, maximum cardiomyocyte necrosis was found to be 1.0 +/- 0.2%. In response to the same parameters (i.e., 5 mg of clenbuterol and sampled at 12 h), skeletal myocyte necrosis was 4.4 +/- 0.8% in the soleus. These data show significant myocyte-specific necrosis in the heart and skeletal muscle of the rat. Such irreversible damage in the heart suggests that clenbuterol may be damaging to long-term health.
PMID: 12381771 [PubMed - indexed for MEDLINE]
Characterization of adrenoceptor involvement in skeletal and cardiac myotoxicity Induced by sympathomimetic agents: toward a new bioassay for beta-blockers.
Tan LB, Burniston JG, Clark WA, Ng Y, Goldspink DF.
Academic Unit of Molecular Vascular Medicine, University of Leeds, England.
Excessive levels of catecholamines have long been known to be cardiotoxic, but less well known are their toxic effects on skeletal muscle. By using an antimyosin monoclonal antibody and quantitative methods to measure the extent of myocyte necrosis, and by employing modulators of adrenoceptors (ARs), including clenbuterol, bupranolol, propranolol, bisoprolol, atenolol, ICI-118551, phenoxybenzamine, prazosin, and yohimbine, the involvement of ARs in isoproterenol-induced myotoxicity was characterized. In the myocardium, the toxic effects were predominantly mediated via the beta(1)-ARs. In the soleus muscle, it was almost solely via the beta(2)-ARs. Myotoxicity was also observed in the myocardium when challenged with the beta(2)-AR agonist clenbuterol. This was found to be mediated via sympathetic presynaptic beta(2)-ARs, leading to enhanced release of norepinephrine. This effect was abolished by prior treatment with reserpine. The skeletal muscle was found to be more sensitive to the myotoxic effects than cardiac muscle at lower doses of beta-AR agonists. These experiments introduce a new way of assaying beta-AR antagonists by classifying them according to their ability to prevent catecholamine-induced myotoxicity. Further research along these lines may deepen understanding of which beta-blockers work best in heart failure therapy.
PMID: 12658052 [PubMed - indexed for MEDLINE]
Dose-dependent separation of the hypertrophic and myotoxic effects of the beta(2)-adrenergic receptor agonist clenbuterol in rat striated muscles.
Burniston JG, Clark WA, Tan LB, Goldspink DF.
Research Institute for Sport & Exercise Sciences, Liverpool John Moores University, Webster Street, Liverpool L3 2ET, UK.
Muscle growth in response to large doses (milligrams per kilogram) of beta(2)-adrenergic receptor agonists has been reported consistently. However, such doses may also induce myocyte death in the heart and skeletal muscles and hence may not be safe doses for humans. We report the hypertrophic and myotoxic effects of different doses of clenbuterol. Rats were infused with clenbuterol (range, 1 mug to 1 mg.kg(-1)) for 14 days. Muscle protein content, myofiber cross-sectional area, and myocyte death were then investigated. Infusions of >/=10 mug.kg(-1).d(-1) of clenbuterol significantly (P < 0.05) increased the protein content of the heart (12%-15%), soleus (12%), plantaris (18%-29%), and tibialis anterior (11%-22%) muscles, with concomitant myofiber hypertrophy. Larger doses (100 mug or 1 mg) induced significant (P < 0.05) myocyte death in the soleus (peak 0.2 +/- 0.1% apoptosis), diaphragm (peak 0.15 +/- 0.1% apoptosis), and plantaris (peak 0.3 +/- 0.05% necrosis), and significantly increased the area fraction of collagen in the myocardium. These data show that the low dose of 10 mug.kg(-1).d(-1) can be used in rats to investigate the anabolic effects of clenbuterol in the absence of myocyte death. Muscle Nerve, 2006.
PMID: 16411205 [PubMed - in process]
http://etd.lsu.edu/docs/available/et...son_thesis.pdf
In rats, a single administration of clenbuterol at or above 10?g/kg produces skeletal muscle necrosis, and doses at or above 100?g/kg induce cardiac necrosis8,10,12. In the heart, this effect is most pronounced in the left ventricle. With repeated administration at or below 10?g/kg in rats, clenbuterol appears to induce muscle hypertrophy without adverse side effects; the attenuation of myotoxic effects over time is thought to be related to downregulation of adrenoreceptors10. Skeletal and cardiac muscle injury was demonstrated in both non-surviving horses. The dose of clenbuterol administered to horse 3 was well below the dose which is reported to induce cardiac necrosis in rats.
Cardiac hypertrophy - thickening (enlarging) of the heart muscle - is a side effect of using clenbuterol demonstrated in animal studies. As well, there have been reports of myocardial infarction, or heart attacks, in humans. In two unrelated cases, 2 otherwise healthy body builders aged only 26 and 17 experienced myocardial infarction from the use of clenbuterol. Various studies have also found that prolonged use actually reduced physical performance of the subjects.
